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Indexed by:期刊论文

Date of Publication:2011-09-01

Journal:JOURNAL OF MOLECULAR GRAPHICS & MODELLING

Included Journals:SCIE、EI

Volume:30

Page Number:67-81

ISSN No.:1093-3263

Key Words:CDK2; Inhibitors; CoMFA; CoMSIA; Molecular docking; Molecular dynamics

Abstract:CDK2 (cyclin-dependent kinase 2) is an attractive target for therapeutic intervention in cancer. In this work, quantitative structure-activity relationship (QSAR), molecular docking, and molecular dynamics (MD) studies were performed on three sets of 155 CDK2 inhibitors. The obtained models exhibit good predictive capability in both internal and external validations (q(2) = 0.73, r(pred)(2) = 0.94 for 6, 6-dimethyl pyrrolo [3,4-c]pyrazoles analogs, q(2) = 0.62, r(pred)(2) = 0.63 for imidazole pyrimidine amides analogs and q(2) = 0.56, r(pred)(2) = 0.58 for 4-(pyrazol-4-yl)-pyrimidines analogs). Furthermore, a comparison between 3D-contour map, docking and MD simulation explore in detail the binding modes and the key structural features impacting the interaction of each series of inhibitors with the CDK2 enzyme, which should be useful to aid the designing of new inhibitors with CDK2 improved biological response. (C) 2011 Elsevier Inc. All rights reserved.